Asthma, or reactive airway disease, is a chronic respiratory disease in which reversible bronchial obstruction and bronchospasm lead to dyspnea, wheezing, chest tightness, and/or cough. Inflammation of the airways is key to the pathogenesis of asthma. Inflammatory cells—including mast cells, eosinophils, T lymphocytes, plasma cells, and basophils—release histamine, various kinins, leukotrienes, prostaglandins, lipid mediators, tumor necrosis factor  (TNF-), neuropeptides, substance P, and a host of other inflammatory mediators. Other features are smooth muscle hypertrophy, edema, basement membrane thickening, and mucous accumulation in airways.

The inflammatory process is triggered by allergens, which play a central role in approximately 60% of asthma patients. Other triggers include respiratory infections, inhaled irritants (particularly tobacco smoke and occupational exposures), gastroesophageal reflux, stress, exercise, cold temperatures, and medications such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and beta-blockers. Asthma is also caused by agents to which a person has specific sensitivity, such as aspirin and tartrazine, which is a petroleum-derived colorant (FD&C Yellow #5).[1]

The prevalence of asthma in the US is approximately 8%. Although the disease commonly begins in childhood, up to 40% of patients develop asthma as adults. Among adult patients, 10-20% have occupational asthma. An increase in the global prevalence of asthma over the past 30 years has been attributed to climate change, allergen exposure, urbanization, and air pollution, among other factors, but the precise pathogenesis of the observed increase is not clear. Asthma is more prevalent in affluent countries, leading to the question of whether overuse of antibiotics has led to reduced bacterial antigen exposure and a shift of the immune system to a more atopic phenotype. Air pollution’s direct contribution to asthma is not clear; certain components may exacerbate asthma.

Risk Factors

In children, asthma occurs more commonly in boys. Among adults, however, the disease is most prevalent in women over 40. Pregnant women with asthma can be divided into three equal groups based on symptom presentation, with a third experiencing worsening of asthma symptoms during pregnancy, a third for whom symptoms remain unchanged, and a third for whom asthma improves. Both mortality and morbidity are greater in Black individuals compared with white. These differences are attributed in part to socioeconomic factors.[2]

Other risk factors include the following:

Atopy. Serum levels of immunoglobulin E (IgE), the antibody most commonly associated with respiratory allergy, appears to be closely linked with airway hyperresponsiveness.

Family history. About 75% of children with 2 asthmatic parents also have asthma.

Environmental and occupational factors. These factors include tobacco smoke, animal dander, dust mites, cockroach allergens, plants, pollen, mold, enzymes, chemicals, and metals.[3]

Body weight. Recent studies suggest that obesity might modify airway smooth muscle function, increasing the risk for developing asthma.[4] In both pediatric and adult populations, increased body weight is directly associated with the odds of incident asthma, suggesting that incidence could be reduced by weight loss.[1][5]

Diagnosis

A characteristic history of periodic bronchospasm and variable airflow obstruction, occurring with or without stimuli that provoke an attack, is usually present. During acute attacks, symptoms such as tachypnea, chest tightness, wheezing, shortness of breath, and cough, with or without sputum production, are common. Difficulty taking deep breaths, finishing sentences, and/or lethargy indicate greater severity, and possibly, status asthmaticus.

Physical examination often reveals use of accessory respiratory muscles, a prolonged expiratory phase with diffuse wheezing, and sometimes hyperresonant lung fields with diminished breath sounds due to air trapping. Severe attacks may have less wheezing (due to reduced air flow), but may result in cyanosis and signs of mental obtundation.

Peak expiratory flow rate (PEFR) can suggest a diagnosis of asthma when below-normal values respond to bronchodilators. In addition, PEFR may be used to diagnose exacerbations.

Routine pulmonary function tests during asymptomatic periods may be entirely normal. During exacerbations or in patients who have had asthma for many years, spirometry typically shows reduced forced expiratory volume in 1 second (FEV1), a reduced FEV1/forced vital capacity (FVC) ratio, and/or reduced peak flows and may also demonstrate increased total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC).

Bronchoprovocation testing is used to assess airway responsiveness. A negative test argues against an asthma diagnosis.Testing can also show the degree of airway hyperresponsiveness and quantify disease severity. Bronchoprovocation can be extremely valuable in those patients who do not present with typical asthma symptoms, but instead may present with nocturnal awakening or chronic cough.

Blood testing may reveal eosinophilia and elevated serum IgE levels in asthma patients with atopy.

Skin testing can identify allergens that may be environmentally controlled.

Medicines such as beta-blockers, NSAIDs, and aspirin may reveal an underlying asthma diagnosis if symptoms are triggered after ingestion.

Treatment

Treatment(s) required to control symptoms and exacerbations defines asthma severity. Asthma is considered well-controlled if current treatment allows for no activity limitations, no waking (nighttime) symptoms, and less than twice weekly use of as-needed medications. Severity is assessed only after several months of regular controlled treatment.[6]

Mild asthma, defined by minimal symptoms and minimal risk of exacerbation can be initially treated on an as-needed basis, preferably with inhaled low-dose corticosteroid (ICS)-formoterol or, when this combination is not an option, with inhaled short-acting beta-2-selective agonists (SABA)-ICS combo, or a SABA alone. The most common ICF-formoterol combo is budesonide-formoterol. The most common SABA is albuterol. The ICS-formoterol combination is a change from historic “as needed” treatment with soley a SABA as this regimen leads to decreased exacerbation risk in all degrees of asthma. If symptoms are not controlled, the regimen is escalated to include a controller medication which is typically a daily or twice daily inhaled ICS. Common steroid preparations include budesonide, fluticasone, triamcinolone, and beclomethasone. As-needed, low-dose ICS-formoterol or SABA can be used to treat exercise-induced broncocontriction in those with or without a diagnosis of asthma.

Moderate asthma is defined by good control with a daily regimen consisting of an inhaled low-dose ICS-long-acting beta-agonist (LABA), low-dose ICS-leukotriene antagonist combination, or medium-dose ICS. Examples of leukotriene antagonists are zileuton, montelukast, and zafirlukast. Sustained-release theophylline and cromolyn are alternatives. Failure to control symptoms with the use of 2 of the above medications suggests the patient may have severe asthma or perhaps another diagnosis.

Severe asthma is defined by the requirement of high-dose ICS with additional controller medications to maintain control of symptoms or the inabily to control symptoms despite these therapies. Adverse effects of inhaled steroids include dysphonia and oral candidiasis (thrush). For this reason, it is advisable to use a spacer with each dose.

Other Treatments

With optimal asthma management, patients should not have symptoms, exercise limitations, exacerbations, or any need for oral steroids or albuterol. Overall, medications and side effects should be minimal.

Leukotriene antagonists are efficacious in a subset of asthma patients and can be considered initial controller medications in carefully selected individuals. Patients with exercise-induced bronchoconstriction, nasal polyposis, and aspirin sensitivity (triad asthma) tend to respond well to these agents. Before prescribing this class of medications, physicians should review the known neuropsychiatric side effects including new-onset nightmares, behavior changes, and, in some cases, suicidal ideation.

Long-acting beta-agonists, such as salmeterol and formoterol, are not to be used as monotherapy, as they have no significant anti-inflammatory effects. Indeed, they cause prolonged bronchodilation, which may mask a progressive inflammatory process that could eventually lead to a severe attack.[7] One study showed a small increase in risk of death among patients, particularly Black individuals, using salmeterol in addition to typical asthma drugs.[8]

Tiotropium, a daily inhaled long-action muscarinic antagonist (LAMA), historically used to treat chronic obstructive pulmonary disease, is FDA approved for long-term maintancence therapy in asthma. It suggested only as an add-on therapy for patients who are not well-controlled with an inhaled ICS-LABA.

Additional therapies for severe asthma or asthma subclasses. Multiple biologic drugs have been developed to target different mechanisms in play among those with severe asthma or those with an eosinophilic phenotype of asthama. These drugs target either IgE, interleukin(IL)-4 receptors, IL-5, IL-5 receptors or thymic stromal lymphopoietin. The safety and utility of these medications depends on several factors including age, serum IgE level, and type 2 asthma phenotype. They should only be prescribed after consultation with a specialist. Biologic drugs include omalizumab, mepolizumab, dupilumab, benralizumab, reslizumab, and tezepelumab.

Theophylline is not considered a first-line agent. However, in combination with inhaled corticosteroids, it may be beneficial.

Cromolyn, which has been historically used as an adjunctive therapy, is no longer recommended.

The 2020 National Asthma Education and Prevention Program guidelines recommend annual administration of influenza vaccine. The pneumococcal vaccine is also recommended in patients with severe asthma and those who require chronic oral glucocorticoid therapy.[9]

Emergency Treatment

Immediate bronchodilation with inhaled albuterol is the mainstay of emergency treatment. In the emergency room, the delivery method for albuterol is most often continuous nebulization (approximately 10 mg/hr), or 2.5 mg every 20 minutes for 3 doses. Data show, however, that using a metered-dose inhaler (with a spacer) for 4-6 successive inhalations is approximately equal to 1 nebulizer. The metered-dose method has the advantages of reducing the total amount of albuterol administered and shortening the length of stay in the emergency department, without increasing hospital admissions.[10] The addition of inhaled ipratropium bromide (an anticholinergic agent) is indicated if a person has moderate to severe airway obstruction that is unresponsive to beta-agonists alone.

Systemic corticosteroids, such as prednisone, prednisolone, and methylprednisolone, should be started concurrently. Their effect is often delayed up to 6 hours and their use is typically continued for at least 5 days after initial dosing to allow for extended treatment of airway inflammation

Heliox can benefit patients with severe airflow obstruction and mild hypoxemia in the acute setting. In patients with severe hypoxemia, the helium concentration should be decreased to a level less than what has been shown to be effective for improving airflow obstruction (70-80% helium) in order to deliver oxygen concentrations needed to maintain normoxia. Therefore, heliox is contraindicated in severe hypoxemia. Moreover, its use should be individualized and is not routinely recommended due to insufficent evidency of efficacy.

Magnesium sulfate, given intravenously, may be tried when a patient does not respond to bronchodilators, but its additional benefits remain debated.

Nutritional Considerations

Roles have emerged for plant-based diets, healthy weight maintenance, modification of fatty acid intake, and avoidance of dairy products, fast food, sugar-sweetened beverages, and excess sodium in the prevention and management of asthma, as described below.

Maintenance of a healthy body weight. A meta-analysis of weight and asthma in children found that being overweight increases the risk for asthma by 35%, while being obese raises the risk by 50% when compared with healthy-weight children.[11] Loss of excess weight results in improved lung function.[12] Also, alternate-day calorie restriction (less than 20% of regular calorie intake days) has been shown to reduce asthma-related symptoms and improve lung functions within 2 weeks of diet initiation.[13]

Modifying fatty acid intake. Omega-6 fatty acids (found in animal products, margarine, and other vegetable oils) may increase the risk for asthma, presumably because the long-chain omega-6 fatty acid arachidonic acid is a precursor of leukotrienes with bronchoconstrictive effects. In contrast, omega-3 fatty acids have anti-inflammatory effects. A high ratio of omega-6 to omega-3 fatty acid intake has been significantly associated with the risk for asthma in a pediatric population.[14]

Clinical evidence shows that a diet high in saturated fat, found in dairy products, red and processed meats, butter, and certain types of oils, negatively affects airway inflammation.[15] Clinical evidence also shows that diets enriched with omega-6 fatty acids hinder the incorporation of omega-3 fatty acids into plasma and tissue lipids.[16]

Studies are conflicting concerning a benefit of omega-3 supplementation in adults with asthma. Some show inhibition of mild airway responses to exercise and eucapnic voluntary hyperventilation, as well as reductions in markers of airway inflammation, while others show no improvement in test-challenged bronchial hyperreactivity, sputum eosinophil counts, or excretion of mast cell mediators in people with mild to moderate asthma.[17]

Avoidance of dairy products. Women who consumed low-fat yogurt once or more per day or low-fat milk 5.5 times or more per week during pregnancy had a 21% and 8% higher risk, respectively, for having a child diagnosed with asthma, when compared with those consuming none.[18] In the French Six Cities Study, a roughly 50% greater asthma prevalence was found in children who consumed butter 3 or more times per week compared with those who consumed butter never or only occasionally.[19]

In a randomized clinical trial of 312 children at risk of atopy (a parent or sibling affected), avoiding cow’s milk formula for at least the first 3 days of life significantly reduced asthma or recurrent wheezing later in life.[20]

Avoidance of fast foods. The International Study of Asthma and Allergies in Childhood (ISAAC) found a nearly 40% greater risk for severe asthma in children and adolescents who consumed fast food 3 or more times per week when compared with those who ate fast food never or only occasionally.[21]

Nut consumption. Although peanuts and tree nuts can be allergenic, the Danish National Birth Cohort study found that the intake of these during pregnancy was inversely related to a diagnosis of asthma in offspring at 18 months of age.[22] In the E3N study of French women, the risk of frequent attacks (defined as 1 or more attacks per week) was lower in women with the highest consumption of nuts and seeds (> 5.3 g/day) than in those with the lowest consumption (≤ 1.0 g/day).[23]

Avoidance of salty foods. A low-sodium diet maintained for 1 to 2 weeks decreased bronchoconstriction in response to exercise in individuals with asthma, but the evidence does not yet support a benefit of a low-sodium diet on either the prevalence or severity of asthma.[24]

Fruits, vegetables, and other foods high in antioxidants. High consumption of fruits and vegetables is associated with decreased risk for asthma in children and adults. Fruits and vegetables have also been shown to improve lung function and make asthma symptoms, including wheezing, more manageable. Researchers suggest that the antioxidants and flavonoids found in plant foods may have a protective effect.[15]

Avoidance of allergenic foods, beverages, and preservatives. Food allergies often precede the development of asthma, and in the National Cooperative Inner-City Asthma Study, 45% of children showed IgE sensitization to at least 1 of the 6 most common food allergens.[25] Food-induced bronchospasm occurs with the intake of certain foods in 2-24% of persons with asthma. Foods implicated most often as a cause include peanuts, milk, eggs, tree nuts, soy, wheat, legumes, beans, and turkey.[26] Most studies report a 3-10% prevalence of sulfite sensitivity among asthmatic subjects, and double-blind, controlled studies have demonstrated that sulfite-containing beverages and foods can cause potentially life-threatening asthmatic reactions in as many as 5% of the asthmatic population.[27][28] Most sulfite-sensitive persons with asthma are steroid-dependent. Avoidance is the most beneficial approach to sulfite sensitivity.[29] Further evidence that food allergy is a risk factor for life-threatening asthma is demonstrated by a substantially higher rate of food allergies in children requiring intubation for asthma compared with controls.[30]

Allergy testing should be considered in patients who appear to experience an exacerbation of asthma with certain foods or food groups. Alternatively, patients can attempt to determine if a particular food triggers asthma by eliminating all common, potentially allergenic foods and then reintroducing them one at a time. Patients should keep careful records of food intake and any change in symptom frequency to confirm that a given food is provoking an exacerbation of asthma.

Vegetarian and vegan diets. In a study of 27,766 Seventh-day Adventists, vegetarian women reported a lower incidence of asthma compared with women on nonvegetarian diets.[31] The theoretical basis for the value of vegan diets is the absence of potential triggers, particularly dairy products and eggs, as well as a relative lack of arachidonic acid. Similarly, Mediterranean diets are associated with a modestly lower risk of developing childhood asthma.[32][33]

Avoidance of sugar-sweetened beverages. In the 2009 Youth Risk Behavior Survey, the odds of having asthma were 28% greater among students who drank regular soda 2 times per day, and 64% greater in those who drank regular soda 3 or more times per day. Previous research studies found that asthma symptoms were worsened by regular soda consumption.[34] The Behavioral Risk Factor Surveillance System found that nonobese adults who consumed 2 or more servings per day of sugar-sweetened beverages had a roughly 65% greater risk for asthma compared with nonconsumers.[35] The risk for asthma in children ages 2 9 was also significantly higher when they consumed either apple juice or high-fructose-corn-syrup-sweetened beverages 5 or more times per week, compared with consuming only 1 per month or less.[36]

Alcohol. Alcohol consumption has a U-shaped association with the development of new-onset asthma in adults.[37]

Vitamin D status. A meta-analysis found that vitamin D deficiency was more common among persons with asthma than control subjects, and was associated with decreased lung function in asthmatic children.[38] Reviews of the possible benefit of vitamin D supplementation, however, have come to varied conclusions; one concluded that the evidence was of poor quality and another concluded that vitamin D-supplemented children had a roughly 25% lower risk for asthma exacerbations when compared with groups without supplemental vitamin D.[39][40]

Preventive measures. Measures recommended to decrease the risk for developing asthma include breastfeeding for the first 4-6 months of life and avoiding the following foods until children reach the specified ages: dairy products until at least 1 year old, eggs until at least 2 years old, and nuts and fish until at least 3 years old.[41]

Orders

See Basic Diet Orders chapter

Smoking cessation.

Avoidance of allergic triggers identified in the patient history.

Vegetarian diet, nondairy, may be tried on a prospective basis.

Weight loss.

What to Tell the Family

Asthma can generally be well-managed with diet and medications. Family members can help by encouraging a diet high in fruits, vegetables, whole grains, and omega-3-rich seeds (e.g., flaxseeds and chia seeds), and avoiding dairy products, eggs, meat, added oils, and processed foods. Adopting such a diet themselves may make it easier for the patient to adhere to the dietary changes.

References